The objectives of this proposal are to define those factors which are involved in the control of utero-placental circulation. By utilizing chronic preparations in pregnant sheep and fetuses, methods have been developed which permit serial blood sampling from and drug administration to either the mother and/or fetus, and the direct measurement of uterine arterial blood flow and its distribution. The areas of interest include the origin and vasomotor effects of endogenous steroids and the circulatory effects of pharmacologic agents employed during pregnancy. Investigation of the endogenous control of utero-placental circulation may provide a description of the role of placental circulation in fetal nutrition and well-being. This would provide further insight into the pathophysiology of fetal malnutrition and changes in utero-placental flow naturally occurring during pregnancy and at the time of labor and delivery. Of particular interest is the correlation between the measurement of uterine blood flow, using the above methods and the quantification of placental function determined by the rate of placental utilization of maternal plasma prehormones. This requires a definition of the origin and physiology of estrogen in this species and will provide an indirect measurement of placental blood flow through an evaluation of the placental clearance of estrogen precursors. This study also will provide information about the endocrine events preceding and after the onset of parturition. The investigation of the vascular effects of commonly employed pharmacologic agents would determine which of these might be harmful to the fetus through their effects on the magnitude and distribution of uterine blood flow. This proposal will also address itself, by virtue of the methodology employed, to alterations in cardiac output and regional blood flows following the administration of pharmacologic compounds, providing further information about the normal cardiovascular physiology of pregnancy and its aberrations.